Statins as pharmaceutically active substances of biopharmaceutical class II (BCS class II) are considered under pharmaceutical aspects as being unstable and are particularly susceptible to oxidative degradation. To avoid this, different methods respectively proceedings are known. These include the suitable choice of the dosage form, the addition of suitable excipients, as well as the selection of a suitable packaging.
In order to reduce the oxidative degradation rate of statins, they are formulated together with antioxidant substances (antioxidants). By the use of the antioxidants as well as other excipients in the mostly oral pharmaceutical composition the active substance is sufficiently stabilized.
The disadvantage thereof is that for stabilization of the active substance redundant measures are possibly taken.
For example, dosage forms known from the prior art have a quantity of excipient, which due to their amount, have an adverse effect on weight and volume of the dosage form and the production costs. The higher the proportion of excipient, the smaller is also the concentration of the active substance within the formulation. Low concentrations of the active substance also have the effect that the ratio of impurities, such as degradation products of the active substance, in relation to the active substance are disadvantageously increased. Therefore, in general, a high concentration of active substance, i.e. a small ratio of excipients in the formulation is sought.
In case of the statins, as an important aspect it appears that the solubility and the dissolution rate of these active substances increases in the physiological system, the higher the proportion of excipients used in the dosage form is.
As statins in connection with the present invention, pharmaceutically active substances are understood which belong to the pharmacological class of compounds of 3-hydroxy-3-methylglutaryl-coenzyme-A-reductase (HMG-CoA reductase) inhibitors.
Statins are mainly used with lipid disorders as cholesterol-lowering agents and exhibit the highest potency when compared to all medications which affects lipid metabolism.
WO 2004/010 933 A (UNIV LELAND STANFORD JUNIOR [U.S.]; KIM SEUNG [U.S.]; Rulifson INGRID [U.S.]; HORI Yuichi [U.S.]) Jul. 27, 2003 discloses a composition which comprises beside a statin a cholesterol absorption inhibitor, here Ezetimibe, and at least one substance stabilizing the active substance.
It is disadvantageous that the composition only has a relatively low proportion of statin and also the combination of statins and the cholesterol absorption inhibitor Ezetimibe, compared with compositions comprising only statins as a pharmaceutically effective ingredient, shows a higher number of serious side effects and thus poorer patient compliance.
KR 20050030282 A (KOREA UNITED PHARM INC) Sep. 25, 2003 discloses a dosage form comprising simvastatin dissolved in a soft capsule.
Adversely in this case turns out to be the high proportion of surface-active substances, which is necessary to control the bioavailability of the statin.
The statins usable in connection with the compositions described in connection with the present invention are defined by their biopharmaceutical class. The biopharmaceutical classification system (BCS) classifies pharmaceutically effective substances in terms of their bioavailability to be expected.
The statins used in the compositions of this invention are classified in the biopharmaceutical class II and have a low solubility at high membrane permeability. The resorption is controlled by the solubility and/or the solution rate of the drugs.